Effects of Febuxostat on Adipokines and Kidney Disease in Diabetic Chronic Kidney Disease
Hyperuricemia is emerging as a risk factor for development of diabetes and metabolic syndrome. Recently, it was shown in in-vitro cell culture experiments that hyperuricemia induces redox-dependent signaling and oxidative stress in adipocytes. By targeting levels of uric acid with febuxostat it is hypothesized that the levels of oxidative stress in adipose tissue (obtained by fat biopsy) will decrease.
Primary aims of the study are to determine whether febuxostat therapy in overweight or obese, diabetic patients with stage 3 Chronic Kidney Disease (CKD) and high serum uric acid levels
- will affect adipose tissue concentrations of thiobarbituric acid reactive substance (TBARS), a marker of oxidative stress
- will affect adipose tissue expression and concentrations of adiponectin; and
- will affect urinary concentrations of transforming growth factor (TGF)- B1.
연구 개요
상세 설명
Hyperuricemia is highly prevalent in the US population and commonly clusters with obesity and metabolic syndrome. It remains controversial whether this reflects an epiphenomenon or connotes a causal role of hyperuricemia in metabolic syndrome. If indeed hyperuricemia plays a causal role in metabolic syndrome, it would be expected that hyperuricemia will impact on the molecular signals that mediate the effects of adiposity on inflammation and insulin resistance.
Adipokines, the protein hormones produced by the adipocytes, serve as the signals for the effects of adipocytes on insulin resistance, dyslipidemia, hypertension, inflammation and atherosclerosis. Adipokines include tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), plasminogen activator inhibitor (PAI-1), leptin, angiotensinogen and adiponectin. In obesity, the production of TNF-α, IL-6, PAI-1, leptin and angiotensinogen increases whereas the production of adiponectin decreases. Increased expression of pro-inflammatory TNF-α and IL-6 and decreased expression of anti-inflammatory adiponectin by adipocytes results in insulin resistance and inflammation.
As oxidative stress in adipose tissue is considered to play a critical role in dysregulation of adipokines production in obesity and that hyperuricemia induces oxidative stress in adipocytes, it is hypothesized that hyperuricemia alters adipose tissue production of adipokines; therefore, febuxostat therapy will decrease hyperuricemia and thereby, have beneficial effects on adipokine production by adipose tissue; the favorable effects on adipokine production by febuxostat therapy will result in decrease in plasma levels of markers of inflammation; and as a result of the above, urinary markers of kidney disease will improve.
Chronic Kidney Disease (CKD) patients with type 2 diabetes will be studies because this population has a high prevalence of hyperuricemia and likely represents a target population which might benefit from reduction of uric acid levels.
This is a placebo-controlled, double-blinded, randomized controlled trial to examine the effects of uric acid lowering with oral febuxostat on adipokines and markers of inflammation.
연구 유형
등록 (실제)
단계
- 해당 없음
연락처 및 위치
연구 장소
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Utah
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Salt Lake City, Utah, 미국, 84112
- University of Utah
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Age > 18 years
- BMI > 25 kg/m2
- type 2 diabetes
- serum uric acid ≥ 5.5 mg/dl in men and ≥ 4.6 mg/dl in women
- eGFR 30-60 mL/min/1.73m2
Exclusion Criteria:
- History of gout
- concurrent use of azathioprine, mercaptopurine, theophylline, allopurinol, thiazolidinediones or warfarin
- concurrent use of metformin
- current antibiotic therapy
- pregnant women
- prisoners
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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활성 비교기: Febuxostat
80 mg/day of febuxostat for 24 weeks
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80 mg/day of febuxostat for 24 weeks
다른 이름들:
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위약 비교기: Placebo
1 placebo tablet per day for 24 weeks
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1 placebo tablet per day for 24 weeks
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change in Thiobarbituric Acid Reactive Substance (TBARS) Concentration in Adipose Tissue From Baseline to 24 Weeks
기간: Baseline and 24 weeks
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The percent difference in thiobarbituric acid reactive substance (TBARS) concentration geometric mean values from baseline to 24 weeks was calculated for each arm
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Baseline and 24 weeks
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Change in Adiponectin Concentration in Adipose Tissue From Baseline to 24 Weeks
기간: Baseline and 24 weeks
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The percent difference in adiponectin concentration geometric mean values from baseline to 24 weeks was calculated for each arm
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Baseline and 24 weeks
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Change in Urinary Concentrations of Transforming Growth Factor-beta1 (TGF-beta1) From Baseline to 24 Weeks
기간: Baseline and 24 weeks
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The percent difference in TGF-beta1 concentration geometric mean values from baseline to 24 weeks was calculated for each arm
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Baseline and 24 weeks
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change in Tumor Necrosis Factor-α (TNF-α) Concentration in Plasma From Baseline to 24 Weeks
기간: Baseline and 24 weeks
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The percent difference in plasma TNF-α concentration geometric mean values from baseline to 24 weeks was calculated for each arm
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Baseline and 24 weeks
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Change in Interleukin-6 (IL-6) Concentration in Plasma From Baseline to 24 Weeks
기간: Baseline and 24 weeks
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The percent difference in plasma IL-6 concentration geometric mean values from baseline to 24 weeks was calculated for each arm
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Baseline and 24 weeks
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Change in High Sensitivity C-Reactive Protein (hsCRP) Concentration in Plasma From Baseline to 24 Weeks
기간: Baseline and 24 weeks
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The percent difference in plasma hsCRP concentration geometric mean values from baseline to 24 weeks was calculated for each arm
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Baseline and 24 weeks
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공동 작업자 및 조사자
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
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